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Method and compostitions for treating coronavirus infection

a technology of coronavirus and compostition, which is applied in the field of antiviral composition, can solve the problems of no commercial therapeutically effective drugs, no prophylactic drugs available to treat ebov (eboval virus) and marv (virus) infections, widespread morbidity and mortality, etc., and achieve the effect of reducing the infectivity of progeny viruses

Active Publication Date: 2020-08-04
PHOENIX BIOTECH INC
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

This patent season describes two methods for treating viral infections. The first method involves using a special antiviral composition to stop the transmission and infection of virus particles released from treated cells. The second method involves chronically administering a cardiac glycoside to inhibit the replication of a coronavirus and reduce the spread of the virus in the body. These methods may offer new ways to prevent and treat virus infections in humans.

Problems solved by technology

Bardoxolone itself has been extensively investigated in clinical trials in inflammatory conditions; however, a Phase 3 clinical trial in chronic kidney disease was terminated due to adverse events that may have been related to known cellular toxicities of certain triterpenoids including bardoxolone at elevated concentrations.
Beyond supportive care or symptomatic treatment, there are no commercial therapeutically effective drugs and no prophylactic drugs available to treat EBOV (Eboval virus) and MARV (Marburg virus) infections, i.e. filovirus infections.
They are found in arthropods, primarily ticks and mosquitoes, and cause widespread morbidity and mortality throughout the world.
Death may result from progressive respiratory failure due to alveolar damage.
Oleandrin has demonstrated anti-HIV activity but has not been evaluated against many viruses.
The antiviral activity of oleandrin, oleanolic acid, ursolic acid and betulinic acid is unpredictable as far as efficacy against specific viruses.
(“A screen of FDA-approved drugs for inhibitors of Zikavirus infection” in Cell Host Microbe (2016), 20, 259-270) report that digoxin demonstrates antiviral activity against Zikavirus but the doses are too high and likely toxic.
Neural damage and subsequent degeneration can cause severe disability in patients with HAM / TSP.
Even though cardiac glycosides have been demonstrated to exhibit some antiviral activity against a few viruses, the specific compounds exhibit very different levels of antiviral activity against different viruses, meaning that some exhibit very poor antiviral activity and some exhibit better antiviral activity when evaluated against the same virus(es).

Method used

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  • Method and compostitions for treating coronavirus infection
  • Method and compostitions for treating coronavirus infection
  • Method and compostitions for treating coronavirus infection

Examples

Experimental program
Comparison scheme
Effect test

example 1

Supercritical Fluid Extraction of Powdered Oleander Leaves

Method A. With Carbon Dioxide.

[0243]Powdered oleander leaves were prepared by harvesting, washing, and drying oleander leaf material, then passing the oleander leaf material through a comminuting and dehydrating apparatus such as those described in U.S. Pat. Nos. 5,236,132, 5,598,979, 6,517,015, and 6,715,705. The weight of the starting material used was 3.94 kg.

[0244]The starting material was combined with pure CO2 at a pressure of 300 bar (30 MPa, 4351 psi) and a temperature of 50° C. (122° F.) in an extractor device. A total of 197 kg of CO2 was used, to give a solvent to raw material ratio of 50:1. The mixture of CO2 and raw material was then passed through a separator device, which changed the pressure and temperature of the mixture and separated the extract from the carbon dioxide.

[0245]The extract (65 g) was obtained as a brownish, sticky, viscous material having a nice fragrance. The color was likely caused by chlorop...

example 2

Hot-Water Extraction of Powdered Oleander Leaves. (Comparative Example)

[0249]Hot water extraction is typically used to extract oleandrin and other active components from oleander leaves. Examples of hot water extraction processes can be found in U.S. Pat. Nos. 5,135,745 and 5,869,060.

[0250]A hot water extraction was carried out using 5 g of powdered oleander leaves. Ten volumes of boiling water (by weight of the oleander starting material) were added to the powdered oleander leaves and the mixture was stirred constantly for 6 hours. The mixture was then filtered and the leaf residue was collected and extracted again under the same conditions. The filtrates were combined and lyophilized. The appearance of the extract was brown. The dried extract material weighed about 1.44 g. 34.21 mg of the extract material was dissolved in water and subjected to oleandrin content analysis using high pressure liquid chromatography and mass spectrometry. The amount of oleandrin was determined to be 3...

example 3

Preparation of Pharmaceutical Compositions

Method A. Cremophor-Based Drug Delivery System

[0251]The following ingredients were provided in the amounts indicated.

[0252]

ReagentPercent of FormulationNameFunction(% w / w)Antiviral compositionActive agent3.7Vitamin EAntioxidant0.1LabrasolSurfactant9.2EthanolCo-solvent9.6Cremophor ELSurfactant62.6Cremophor RH40Surfactant14.7

[0253]The excipients were dispensed into ajar and shook in a New Brunswick Scientific C24KC Refrigerated Incubator shaker for 24 hours at 60° C. to ensure homogeneity. The samples were then pulled and visually inspected for solubilization. Both the excipients and antiviral composition were totally dissolved for all formulations after 24 hours.

Method B. GMO / Cremophor-Based Drug Delivery System

[0254]The following ingredients were provided in the amounts indicated.

[0255]

ReagentPercent of FormulationNameFunction(% w / w)antiviral compositionActive agent4.7Vitamin EAntioxidant0.1LabrasolSurfactant8.5EthanolCo-solvent7.6Cremophor ...

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Abstract

A method of treating viral infection, such as viral infection caused by a virus of the Coronaviridae family, is provided. A composition having at least oleandrin is used to treat viral infection.

Description

CROSS-REFERENCE TO EARLIER FILED APPLICATIONS[0001]The present application claims the benefit of provisional applications No. 63 / 002,735 filed Mar. 31, 2020, No. 63 / 010,246 filed Apr. 15, 2020, No. 63 / 014,294 filed Apr. 23, 2020, No. 63 / 017,263 filed Apr. 29, 2020, No. 63 / 021,512 filed May 7, 2020, No. 63 / 029,530 filed May 24, 2020, and No. 63 / 034,800 filed Jun. 4, 2020; and the present application claims the benefit of and is a continuation-in-part of Ser. No. 16 / 825,063 filed Mar. 20, 2020, which is a continuation of Ser. No. 16 / 815,260 filed Mar. 11, 2020, which is a continuation of Ser. No. 16 / 803,488 filed Feb. 27, 2020, which is a continuation of Ser. No. 16 / 779,840 filed Feb. 3, 2020, which is a continuation of Ser. No. 16 / 747,637 filed Jan. 21, 2020, which is a continuation of application Ser. No. 16 / 424,902 filed May 29, 2019, which is a continuation-in-part of application Ser. No. 16 / 276,063 filed Feb. 14, 2019, now U.S. Ser. No. 10 / 596,186 issued Feb. 24, 2020, which is a...

Claims

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Application Information

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Patent Type & Authority Patents(United States)
IPC IPC(8): A61K36/24A61K31/7048A61P31/14A61K31/56
CPCA61K36/24A61K31/56A61K31/7048A61P31/14A61K2236/37A61K2236/39A61K2236/00A61K31/704
Inventor NEWMAN, ROBERT A.ADDINGTON, OTIS C.
Owner PHOENIX BIOTECH INC
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